ObjectiveThe pallidonigroluysian (PNL) system, the primary component of corticosubcortical circuits, is generally spared in amyotrophic lateral sclerosis (ALS). We evaluated the clinicopathological features of an unusual form of ALS with PNL degeneration (PNLD) and assessed whether ALS with PNLD represents a distinct ALS subtype.MethodsFrom a cohort of 97 autopsied cases of sporadic ALS with phosphorylated 43kDa TAR DNA‐binding protein (TDP‐43) inclusions, we selected those with PNLD and analyzed their clinicopathological features.ResultsEleven cases (11%) that showed PNLD were divided into 2 subtypes depending on the lesion distribution: (1) extensive type (n = 6), showing widespread TDP‐43 pathology and multisystem degeneration, both involving the PNL system; and (2) limited type (n = 5), showing selective PNL and motor system involvement, thus being unclassifiable in terms of Brettschneiderʼs staging or Nishihiraʼs typing of ALS. The limited type showed a younger age at onset and predominant PNLD that accounted for the early development of extrapyramidal signs. The limited type exhibited the heaviest pathology in the subthalamus and external globus pallidus, suggesting that TDP‐43 inclusions propagated via indirect or hyperdirect pathways, unlike ALS without PNLD, where the direct pathway is considered to convey TDP‐43 aggregates from the cerebral cortex to the substantia nigra.InterpretationThe PNL system can be involved in the disease process of ALS, either nonselectively as part of multisystem degeneration, or selectively. ALS with selective involvement of the PNL and motor systems exhibits unique clinicopathological features and TDP‐43 propagation routes, thus representing a distinct subtype of ALS. ANN NEUROL 2020;87:302–312

To investigate the effect of aging on the oligodendrocyte progenitor cells (OPCs) after cerebral ischemia, neuron-glia antigen 2 (NG2) chondroitin sulfate proteoglycan was examined at 1, 3 and 7 days after 90 min of transient middle cerebral artery occlusion in young and aged brains. The number of NG2 positive cells increased in the ischemic penumbra at 3 and 7 days after reperfusion, while those decreased in the ischemic core. At 7 days, the number of NG2 positive cells was significantly greater in the young than the aged brains, and the processes of NG2 positive cells enlarged and were highly branched in the young than the aged brains. These results suggest that the young brain showed a higher potential of proliferation and process branching of OPCs than the aged brains.

Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is a rare progressive neurodegenerative disease caused by either homozygous or compound heterozygous mutations in the SACS gene. The original ARSACS cases found in Quebec showed very homogenous phenotypes characterized by cerebellar ataxia, spasticity, and polyneuropathy. However, many cases with atypical phenotypes have been found in other regions and ethnic groups. We herein present a Japanese patient with atypical ARSACS who showed cerebellar ataxia and polyneuropathy, but no spasticity. She carried novel compound heterozygous mutations (p.Lys4326 Glu and p.Leu1412Lysfs*16) in the SACS gene. The brain MRI findings were useful for making a diagnosis of ARSACS.

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